32 Tirasak Pasharawipas
However, there is another kind of temperate phage in which its genome
locates in the bacterial cell like a plasmid, without chromosomal integration as
the ordinary temperate phages do. This means the phage genome does not
insert its genome into the bacterial chromosome but localizes extra-
chromosomally or plasmid-like in the bacterial cell (Kawakami and Landman,
1968; Khemayan et al., 2006; Pasharawipas et al., 2008). The previous study
of Khemayan et al. (2006) called the lysogen with an extra-chromosomal
phage genome as true lysogen (TL). The researchers also showed that the sub-
cultural colony of TL by an isolation technique can produce another kind of
lysogen which is called pseudolysogen (PL). The PL is proven to generate
from TL but does not contain any phage genome in its cytoplasm (Khemayan
et al., 2006). It is hypothesized that PL is derived from the TL by the
unequivalent division of the lysogenic chromosome. Since the speeds of
genomic duplication of the phage genome and the bacterial chromosome do
not replicate simultaneously during the binary fission of the TL, the process
erroneously produce PL, besides the TL (Pashrawipas et al., 2008).
Usually, TL can prevent itself from super-infection of the same kind of
phage (Dimmock et al., 2001). This is a well-known phenomenon although the
clear explanation for its mechanism is not well accepted. Surprisingly, the PL
can also prevent itself from super-infection as the TL does although the phage
genome does not really exist in the bacterial cell (Pashrawipas et al., 2008).
Besides the toleration of phage to super-infection as found in lysogenic
bacteria, it is also found in viral infected eukaryotic cells. The mechanism for
this has been proposed with a few different hypotheses. For example, it was
explained by the appearance of defective phages (Cambell, 1960), the role of
cytokines (Sidahmed et al., 2007), gene mutation (Skurnik and Strauch, 2006)
and disappearance of viral receptor molecules (Skurnik and Strauch 2006,
Pasharawipas et al., 2008).
Apparently, the toleration of lysogen, either true lysogen or
pseudolysogen, to re-infection by the same phage is one of problems for the
phage therapy. Thus, to make the concept of phage therapy promising, it is
more appropriate to use virulent phage for the phage therapy to avoid
lysogenic infection. However, our previous study demonstrated that using
temperate phage to treat bacterium is possible with the key consideration of
bacterium-phage ratio, so called MOI (multiplicity of infection).